Recent mechanical studies conducted in my lab at PSU Abington College in the spring of 1998 showed that GABA exerted an inhibitory control over ACh-induced contractions of holothurian smooth muscle. GABA and GABA agonists caused dose-dependent relaxation, while conversely, GABA antagonists stimulated contractions. Whether the GABA receptors lie on the pre-synaptic neurons innervating the muscle, or post-synaptically on the muscle cells themselves remains to be seen but what was clear was that the smooth muscle was responsive to both GABA A and B receptors drugs. Experiments conducted at the BRC in the July 1998 using self-referencing calcium electrodes directly mirrored those aforementioned mechanical studies so that a correlation could be made between sarcolemmal calcium flux and muscle contractility in response to treatment with ACh, GABA and the GABA A and B receptor antagonists/agonists. The first series of experiments at the BRC using the calcium-selective electrodes showed that calcium flux stimulated by ACh was reduced treatment with GABA. This data was in concert with my earlier mechanical data revealing that ACh-induced contractions were reduced by roughly 20% by GABA treatment. Baclofen, a GABA B agonist, similarly reduced ACh-induced calcium flux. One reported mechanism by which GABA and baclofen acts is by stimulating the Ca-dependent K channel, a channel blocked by the action of apamin (bee venom). Treatment with apamin greatly reduced the effectiveness of GABA or baclofen as measured by the calcium-selective electrodes. Treatment with phaclofen, a GABA B receptor antagonist, reduced the activity of both GABA and baclofen (like apamin) which strongly suggests the presence of GABA B receptors in regulating the contractility of the LMBW. 2-hydroxysaclofen or phaclofen (both GABA B antagonists) stimulated calcium flux; this implies that these antagonists either blocked GABA receptors on the muscle itself thus rendering the muscle more excitable, or that they blocked GABA receptors on cholinergic motor neurons upstream thereby releasing them from tonic inhibition and resulting in more ACh release at the neuromuscular junction. Mechanical studies showed that GABA A receptor antagonist, bicuculline, caused a huge sustained contraction of the LMBW. Corroborating this finding with the calcium-selective electrodes, bicuculline stimulated a large calcium flux that was suppressed by treatment with GABA. Conclusive data could not be obtained from experiments with muscimol, a GABA A agonists, as it appeared to destablize the electrode.